Simultaneous determination of oxacillin and cloxacillin in plasma and CSF using turbulent flow liquid chromatography coupled to high-resolution mass spectrometry: Application in therapeutic drug monitoring.

Cloxacillin and oxacillin are group M penicillins. The therapeutic monitoring of plasma concentrations of these antibiotics and those of their hydroxymethylated metabolites is of great clinical interest, especially in the choice of an adequate dosage allowing an effective treatment while limiting the occurrence of undesirable effects and the development of bacterial resistance. In this context, we conducted this work aiming at developing and validating a method allowing the determination of cloxacillin and oxacillin as well as the identification of their active metabolites in different biological matrices (CSF and plasma) using turbulent flow liquid chromatography coupled to high-resolution mass spectrometry.

Elimination of cefotaxime using polysulfone and polyacrylonitrile-derived filters: An assessment.

Continuous renal replacement therapy (CCRT) efficiently eliminates cefotaxime. To our knowledge, there are no previous studies dealing with the disposition of cefotaxime. We studied the elimination of cefotaxime by two filters in a model mimicking a session of CRRT using the NeckEpur technology.

Chronic consumption of Annona muricata juice triggers and aggravates cerebral tau phosphorylation in wild-type and MAPT transgenic mice.

In the pathogenesis of tauopathies, genetic and environmental factors have been identified. While familial clustering led to the identification of mutations in MAPT encoding the microtubule-associated protein tau, the high incidence of a sporadic tauopathy endemic in Guadeloupe was linked to the plant-derived mitochondrial complex I inhibitor annonacin. The interaction of both factors was studied in the present work in a realistic paradigm over a period of 12 months.

Identification of the environmental neurotoxins annonaceous acetogenins in an Annona cherimolia Mill. Alcoholic Beverage Using HPLC-ESI-LTQ-Orbitrap.

Epidemiological and toxicological studies have suggested Annonaceaeous acetogenins to be environmental neurotoxins responsible for sporadic atypical parkinsonism/dementia in tropical areas. These compounds are present in the tropical genus Annona (Annonaceae), known for its fruit-yielding cultivated species such as Annona cherimolia. This species is widely cultivated in South America, Spain, and Portugal and yields acetogenins in its seeds, stems, and roots.

Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4.

Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs.

Natural aristolactams and aporphine alkaloids as inhibitors of CDK1/cyclin B and DYRK1A.

In an effort to find potent inhibitors of the protein kinases DYRK1A and CDK1/Cyclin B, a systematic in vitro evaluation of 2,500 plant extracts from New Caledonia and French Guyana was performed. Some extracts were found to strongly inhibit the activity of these kinases. Four aristolactams and one lignan were purified from the ethyl acetate extracts of Oxandra asbeckii and Goniothalamus dumontetii, and eleven aporphine alkaloids were isolated from the alkaloid extracts of Siparuna pachyantha, S.

Comprehensive characterization of Annonaceous acetogenins within a complex extract by HPLC-ESI-LTQ-Orbitrap® using post-column lithium infusion.

Annonaceous acetogenins (AAGs) are a homogenous class of polyketides proposed as environmental neurotoxins. Previous dereplication studies of AAGs were limited by the use of low-resolution mass spectrometers. Only poor information in terms of structures was provided due to the limited fragmentation of protonated or sodium cationized species.

Structural study of acetogenins by tandem mass spectrometry under high and low collision energy.

Collision-induced dissociation experiments of seven annonaceous acetogenins were carried out under high and low collision energy conditions. Each compound was studied as protonated or deprotonated and lithium- or sodium- cationized molecules, using ElectroSpray Ionisation (ESI) with a hybrid linear trap/orbitrap mass spectrometer (LTQ-Orbitrap®). The same ion species were studied with a Matrix-Assisted Laser Desorption Ionisation (MALDI) tandem mass spectrometer in a high collision energy regime (1 or 2 keV).